Exposure Assessment Core 7.1.1 Goals As noted throughout the application, the overall mission of the UM NIEHS Center is to promote translational research using novel multi-disciplinary approaches to better understand the impact of environmental exposures on selected adult diseases through mechanisms involving epigenetic modifications during vulnerable stages of life. The Exposure Assessment Core supports this mission by facilitating the design, implementation and analysis of exposure assessment activity, with the overall goal of ensuring that exposure assessments and analytical data generated are scientifically sound, guality assured and reflect state -of-the-art knowledge and expertise. Please note that italicized text is used throughout to mark notable updates and revislon(s), including excerpts of critiques and our associated responses. The Core consists of four laboratories and a modeling group, namely: 1. Organic Chemistry Laboratory; 2. Trace Metals Laboratory; (3) Environmental & Molecular Microbiology Laboratory; (4) Nutrition Assessment Laboratory; and (5) Exposure Modeling and Translation. These components support a broad range of collaborative research that includes exposures to metals, organics, particles, and nutrients. Additionally, we will provide referral, coordination and quality assurance (QA) services and consultations regarding study design related to exposure indicators; assistance with sampling, processing, analysis and storage of samples; referral services to supporting laboratories for analytes not measured by the Core itself; data interpretation; and exposure modeling. Overall, the Core will coordinate existing facilities and personnel, promote efficiencies, and expand capabilities to realize the activities and priorities ofthe Center's strategic goals. While we recognize that research examining the impacts of diet on disease is not consistent with NIEHS' mission, nutritional status and nutrient intake can substantially modify susceptibility to environmental toxicants. Such interactions also are relevant to the research of several Center members: S.K. Park's work on dietary anti-oxidants as a modifier of air pollution impacts on cardiovascular disease (e.g.. Park et al., 2009); H. Hu's NIEHS Superfund Project (2000-2006, P01ES05947) Controlled Trial in Pregnancy of Dietary Supplements for the Suppression of Bone Resorption and Mobilization of Lead into Plasma; and J.R. Pilsner's NIEHSsupported research on folate, a methyl-donor affecting global DNA methylation, on arsenic's impact of genomic DNA methylation (Pilsner et al., 2007). The Core Co-Leader in this area, K. Peterson, is an experienced nutrition scientist who has examined nutrient-toxicant interactions (Hernandez-Avila et al., 2003; Arora et al., 2008; Ettinger et al., 2009), and effects on physical growth and development (Gonzalez-Gossio et al., 1997; Gomaa et al., 2002; Peterson et al., 2004). Biological Responses Core 7.2.1 Objectives As noted throughout the application, the overall mission of the University of Michigan NIEHS Center is to promote new translational research using novel multi-disciplinary approaches to better understand the impact of environmental exposures on selected disease processes through mechanisms involving epigenetic modifications during vulnerable stages of life. The overall goal ofthe Biological Responses Core is to provide assistance in the design and implementation of studies associated with the UM NIEHS Center that use freshly collected or archived biological samples to investigate changes to the epigenome or genome that, in turn, are likely to result in changes in gene expression or function and influence disease phenotypes. The Core facility serves as a conduit to other University resources through the Biomedical Research Cores, as well as the analysis of biomarkers of oxidation / oxidative stress, inflammation, cytokines, DNA adducts, etc. The Core supports consultative services in three areas: Epigenetics, Mutation Detection, and Biologic Modeling. Please note that Italicized text Is used throughout to mark notable updates and revision(s), including excerpts of critiques and our associated responses. We are grateful that the previous reviewers were highly enthusiastic about our original proposal for the Biological Responses Core and Its integration within the Center, Combined, these cores will provide multidisciplinary, holistic support for Center-wide research In a fashion where their sum is greater than the parts. These cores represent a clear strength ofthe proposal. Leadership was described as excellent and first rate. We appreciate the opportunity to fine-tune our proposal and respond to several helpful critiques. These Core facilities and consultative services support a broad range of expensive technology and highly specialized services that are better served institutionally rather than within individual laboratories. Profound gains in efficiency and technical expertise are harnessed with this organizational structure. The proposed University of Michigan NIEHS Center (UM NIEHS Center) has already developed an extensive and impressive array of services for new center members by taking advantage ofthe strength of existing Cores and investing in the development of new services and equipment.